![]() ![]() In extracellular field recordings from CA3–CA1 synapses in stratum radiatum, hCSF caused a large increase in evoked excitatory synaptic transmission that was accompanied by an apparent increase in presynaptic release probability (Figure 2K). Moreover, hCSF depolarized the resting membrane potential of CA1 pyramidal cells (Figures 2A,C) and lowered their firing threshold (Figures 2E,F) through apparent G-protein signaling-dependent mechanisms (Figures 2D,G), leading to a left shifted frequency-current (input–output) relationship (Figures 2H–J). In whole-cell patch clamp recordings from CA1 pyramidal cells, hCSF caused a strong increase in neuronal excitability, boosting spontaneous action potential (AP) firing approximately fivefold (Figures 2A,B). A matched aCSF was then designed based on obtained measurements and used as control for potential neuromodulatory effects of hCSF on hippocampal neurons. The study measured electrolyte and glucose levels in pooled samples of hCSF obtained by lumbar puncture from both neurological patients and healthy volunteers. (2015) used the simplistic make-up of aCSF to establish the functional impact of endogenous neuromodulators in real brain extracellular fluid, i.e., human CSF (hCSF), on rat hippocampal neurons. Of particular relevance with respect to neuronal activity and function, physiological CSF is also known to contain a wide range of neuromodulators (Table 1) whose collective influence on cellular and synaptic properties has been poorly investigated. Consisting simply of electrolytes, glucose and water, aCSF lacks the complex organic make-up of physiological CSF including proteins, peptides, lipids, amino acids, etc. However, a limitation of this experimental model is that neurons in brain slices are perfused with artificial extracellular fluid (artificial CSF, aCSF) during recordings. Since its introduction in the early 1970s, the hippocampal brain slice preparation has remained a major in vitro platform to study synaptic, cellular and network aspects of neuronal activity ( Skrede and Westgaard, 1971). Recent in Vitro Findings with Human Cerebrospinal Fluid Electrophysiological Recordings from Rat Hippocampal Brain Slices The potential significance of this neuromodulation is discussed in health and disease, and an outlook on the future advancement of this research field is provided. In this review, we summarize a set of new experimental findings in vitro showing that endogenous neuromodulators in human CSF potently influence the function of pyramidal cells and interneurons in the rat hippocampal brain slice, and in rat cortical neuronal cultures. However, whether the CSF system in fact plays an active, rather than simply passive, role in distributing neuromodulators throughout the brain is still unknown. Here we briefly summarize these new findings and discuss their potential relevance to neural circuits in health and disease.Ĭommunicating freely with the ISF ( Brightman and Palay, 1963 Smith et al., 2004), the CSF system has the potential to serve as a vessel for neuromodulatory signals acting via volume transmission ( Agnati et al., 1986, 2010). Recent in vitro experimental work in brain slices and neuronal cultures has shown that human CSF indeed contains neuromodulators that strongly influence neuronal activity. As such, the CSF is well positioned to actively distribute neuromodulators to neural circuits in vivo via volume transmission. The cerebrospinal fluid (CSF) occupies the brain’s ventricles and subarachnoid space and, together with the interstitial fluid (ISF), forms a continuous fluidic network that bathes all cells of the central nervous system (CNS). 6United Kingdom Dementia Research Institute, University College London, London, United Kingdom. ![]() 5Department of Molecular Neuroscience, UCL Institute of Neurology, University College London, London, United Kingdom.4Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden.3Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.2Department of Neuroscience, Brown University, Providence, RI, United States.1Department of Physiology, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.Andreas Bjorefeldt 1,2* Sebastian Illes 1 Henrik Zetterberg 3,4,5,6 Eric Hanse 1 ![]()
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